Our studies have disclosed that glucocorticoids directly affect neuronal function. These steroids increase the excitability of mammalian motor nerve terminals, preserve functions of traumatized and neurotoxic motor and sensory nerves, augment transmission in segmental spinal reflex pathways and selectively enhance the high-affinity choline uptake in putamen-caudate synaptosomes. We will study the effects of single doses and an intensive regimen of glucocorticoids on the ultrastructure of the neuromuscular junctions in normal animals. The neuromuscular junctions of animals started on an intensive glucocorticoid regimen after exposure to diisopropylfluorophosphate (DFP), an organophosphorous compound which induces a delayed neuropathy, will also be morphologically studied. The motor nerve terminal stimulus-bound repetitive function will also be studied in these glucocorticoid-treated DFP cats. We also plan to investigate the pharmacological differences between phasic and tonic terminals. These differences may be related to nicotinic-like receptors which data from preliminary experiments locate at motor nerve terminal membrane. Since tonic and phasic motoneurons have important functional and trophic differences, their terminals may have similar differences which may not only affect drug action at those junctions but have broad significance for pharmacologic susceptibilities of other synapses. The proposed research has both basic and clinical relevance.